The objective of this study is to delineate, at the cellular and molecular level, the genesis of the humoral anti-erythrocyte autoantibody response -- the primary pathogenetic effector of autoimmune hemolytic anemia. These studies, utilizing NZB mice, include: 1) purification and biochemical characterization of the pathogenetic erythrocyte X autoantigen; 2) delineation of the role of the X autoantigen molecule in the initiation, regulation and genetic segregation of the antierythrocyte autoantibody response; 3) characterization of the B lymphocyte subsets that produce anti-X autoantibody; 4) identification of the idiotypes of the anti-X autoantibody response; and 5) delineation of the genetics of the B cell defect, namely is there deletion of the acceptor site for T suppressor cells, thus rendering these cells permissive for the autoantibody response which mediates autoimmune hemolytic anemia.